The EPH/Ephrin System in Colorectal Cancer

The EPH/ephrin system constitutes a bidirectional signaling pathway comprised of a family of tyrosine kinase receptors in tandem with their plasma membrane-bound ligand (ephrins). Its significance in a wide variety of physiologic and pathologic processes has been recognized during the past decades. In carcinogenesis, EPH/ephrins coordinate a wide spectrum of pathologic processes, such as angiogenesis, vessel infiltration, and metastasis. Despite the recent advances in colorectal cancer (CRC) diagnosis and treatment, it remains a leading cause of death globally, accounting for 9.2% of all cancer deaths. A growing body of literature has been published lately revitalizing our scientific interest towards the role of EPH/ephrins in pathogenesis and the treatment of CRC. The aim of the present review is to present the recent CRC data which might lead to clinical practice changes in the future

Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder

Background: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses of female CD. Methods: As part of the FemNAT-CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9–18 years), compared to 864 sex- and age-matched typically developing controls. Results: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post-traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention-deficit/hyperactivity disorder. In line with the ‘gender paradox’ hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age-of-onset subtypes of CD (i.e. fewer girls with childhood-onset CD). In line with the ‘delayed-onset pathway’ hypothesis, girls with adolescent-onset CD showed similar levels of dimensional psychopathology like boys with childhood-onset CD, while boys with adolescent-onset CD had the lowest levels of internalizing psychopathology. Conclusions: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually developed CD during adolescence. These novel data on sex-specific clinical profiles of CD will be critical in informing intervention and prevention programmes

Investigating sex differences in emotion recognition, learning, and regulation among youths with conduct disorder

Objective: Conduct disorder (CD) is a serious neurodevelopmental disorder marked by notably higher prevalence rates for boys than girls. Converging evidence suggests that CD is associated with impairments in emotion recognition, learning, and regulation. However, it is not known whether there are sex differences in the relationship between CD and emotion dysfunction. Prior studies on emotion functioning in CD have so far been underpowered for investigating sex differences. Therefore, our primary aim was to characterize emotion processing skills in a large sample of girls and boys with CD compared to typically developing controls (TDCs) using a comprehensive neuropsychological test battery. Method: We included 542 youths with CD (317 girls) and 710 TDCs (479 girls), 9 to 18 years of age, from a European multisite study (FemNAT-CD). Participants completed three experimental tasks assessing emotion recognition, learning, and regulation, respectively. Data were analyzed to test for effects of group and sex, and group-by-sex interactions, while controlling for potentially confounding factors. Results: Relative to TDCs, youths with CD showed impaired emotion recognition (that was related to more physical and proactive aggression, and higher CU traits), emotional learning (specifically from punishment), and emotion regulation. Boys and girls with CD, however, displayed similar impairments in emotion processing. Conclusion: This study provides compelling evidence for a relationship between CD and deficient neurocognitive functioning across three emotional domains that have previously been linked to CD etiology. However, there was no support for sex-specific profiles of emotion dysfunction, suggesting that current neurocognitive models of CD apply equally to both sexes